Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea

Liam J. Skinner, Véronique Enée, Maryline Beurg, Hak Hyun Jung, Allen F. Ryan, Aziz Hafidi, Jean Marie Aran, Didier Dulon

Research output: Contribution to journalArticle

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Abstract

Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant τ ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs.

Original languageEnglish
Pages (from-to)320-332
Number of pages13
JournalJournal of Neurophysiology
Volume90
Issue number1
Publication statusPublished - 2003 Jul 1
Externally publishedYes

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels
Cochlea
Synaptic Transmission
Guinea Pigs
Inner Auditory Hair Cells
Outer Auditory Hair Cells
Charybdotoxin
Spiral Ganglion
Cochlear Nerve
Barium
Action Potentials
In Situ Hybridization
Neurotransmitter Agents
Vertebrates
Perfusion
Immunohistochemistry
Ions
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Skinner, L. J., Enée, V., Beurg, M., Jung, H. H., Ryan, A. F., Hafidi, A., ... Dulon, D. (2003). Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea. Journal of Neurophysiology, 90(1), 320-332.

Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea. / Skinner, Liam J.; Enée, Véronique; Beurg, Maryline; Jung, Hak Hyun; Ryan, Allen F.; Hafidi, Aziz; Aran, Jean Marie; Dulon, Didier.

In: Journal of Neurophysiology, Vol. 90, No. 1, 01.07.2003, p. 320-332.

Research output: Contribution to journalArticle

Skinner, LJ, Enée, V, Beurg, M, Jung, HH, Ryan, AF, Hafidi, A, Aran, JM & Dulon, D 2003, 'Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea', Journal of Neurophysiology, vol. 90, no. 1, pp. 320-332.
Skinner, Liam J. ; Enée, Véronique ; Beurg, Maryline ; Jung, Hak Hyun ; Ryan, Allen F. ; Hafidi, Aziz ; Aran, Jean Marie ; Dulon, Didier. / Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the guinea pig cochlea. In: Journal of Neurophysiology. 2003 ; Vol. 90, No. 1. pp. 320-332.
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